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https://www.readbyqxmd.com/read/28096270/mutation-enrichment-next-generation-sequencing-for-quantitative-detection-of-kras-mutations-in-urine-cell-free-dna-from-patients-with-advanced-cancers
#1
Takeo Fuji, Afsaneh Barzi, Andrea Sartore-Bianchi, Andrea Cassingena, Giulia Siravegna, Daniel Karp, Sarina Piha-Paul, Vivek Subbiah, Apostolia M Tsimberidou, Helen Huang, Sillvio Veronese, Federica Di Nicolantonio, Sandeep C Pingle, Cecile Rose T Vibat, Saege Hancock, David Berz, Vladislava O Melnikova, Mark G Erlander, Rajyalakshmi Luthra, Scott Kopetz, Funda Meric-Bernstam, Salvatore Siena, Heinz-Josef Lenz, Alberto Bardelli, Filip Janku
PURPOSE: Tumor-derived cell-free DNA (cfDNA) from urine of patients with cancer offers non-invasive biologic material for detection of cancer-related molecular abnormalities such as mutations in Exon 2 of KRAS. EXPERIMENTAL DESIGN: A quantitative, mutation-enrichment next-generation sequencing test for detecting KRASG12/G13 mutations in urine cfDNA was developed and results were compared to clinical testing of archival tumor tissue and plasma cfDNA from patients with advanced cancer...
January 17, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28096087/diffuse-large-b-cell-lymphoma-genotyping-on-the-liquid-biopsy
#2
Davide Rossi, Fary Diop, Elisa Spaccarotella, Sara Monti, Manuela Zanni, Silvia Rasi, Clara Deambrogi, Valeria Spina, Alessio Bruscaggin, Chiara Favini, Roberto Serra, Antonio Ramponi, Renzo Boldorini, Robin Foa', Gianluca Gaidano
Accessible and real-time genotyping for diagnostic, prognostic or treatment purposes is increasingly impelling in diffuse large B-cell lymphoma (DLBCL). Cell-free DNA (cfDNA) is shed into the blood by tumor cells undergoing apoptosis and can be used as source of tumor DNA for the identification of DLBCL mutations, clonal evolution, and genetic mechanisms of resistance. Here we aimed at tracking the basal DLBCL genetic profile and its modification upon treatment using plasma cfDNA. Ultra-deep targeted next generation sequencing of pre-treatment plasma cfDNA from DLBCL patients correctly discovered DLBCL-associated mutations that were represented in >20% of the alleles of the tumor biopsy with a >90% sensitivity and a ~100% specificity...
January 17, 2017: Blood
https://www.readbyqxmd.com/read/28093244/novel-mutations-on-egfr-leu792-potentially-correlate-to-acquired-resistance-to-osimertinib-in-advanced-nsclc
#3
Kai Chen, Fei Zhou, Wenxiang Shen, Tao Jiang, Xue Wu, Xiaoling Tong, Yang W Shao, Songbing Qin, Caicun Zhou
Osimertinib is an irreversible third generation EGFR tyrosine kinase inhibitor (TKI) and has shown outstanding performances in treating EGFR T790M-positive advanced non-small cell lung cancer (NSCLC) patients, but acquired resistance is inevitable. EGFR C797S is the most notable resistance mechanism to this drug, but other EGFR mutations may also exist. In three lung adenocarcinoma patients resistant to osimertinib, we identified recurrent novel mutations at EGFR Leu792 codon by targeted next generation sequencing (NGS) of cell free DNA (cfDNA) from plasma or pleural effusion...
January 13, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28081183/circulating-cell-free-dna-in-dogs-with-mammary-tumors-short-and-long-fragments-and-integrity-index
#4
Giorgia Beffagna, Alessandro Sammarco, Chiara Bedin, Chiara Romualdi, Marta Mainenti, Antonio Mollo, Laura Cavicchioli, Silvia Ferro, Davide Trez, Raffaella De Maria, Donato Nitti, Andrea Saccani, Michelangelo Campanella, Marco Agostini, Valentina Zappulli
Circulating cell-free DNA (cfDNA) has been considered an interesting diagnostic/prognostic plasma biomarker in tumor-bearing subjects. In cancer patients, cfDNA can hypothetically derive from tumor necrosis/apoptosis, lysed circulating cells, and some yet unrevealed mechanisms of active release. This study aimed to preliminarily analyze cfDNA in dogs with canine mammary tumors (CMTs). Forty-four neoplastic, 17 non-neoplastic disease-bearing, and 15 healthy dogs were recruited. Necrosis and apoptosis were also assessed as potential source of cfDNA on 78 CMTs diagnosed from the 44 dogs...
2017: PloS One
https://www.readbyqxmd.com/read/28079901/the-clinical-utility-of-dna-based-screening-for-fetal-aneuploidy-by-primary-obstetrical-care-providers-in-the-general-pregnancy-population
#5
Glenn E Palomaki, Edward M Kloza, Barbara M O'Brien, Elizabeth E Eklund, Geralyn M Lambert-Messerlian
OBJECTIVE: To assess the clinical utility of cell-free DNA (cfDNA)-based screening for aneuploidies offered through primary obstetrical care providers to a general pregnancy population. METHODS: Patient educational materials were developed and validated and providers were trained. Serum was collected for reflexive testing of cfDNA failures. Providers and patients were surveyed concerning knowledge, decision making, and satisfaction. Pregnancy outcome was determined by active or passive ascertainment...
January 12, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/28063009/dna-methylation-signatures-in-circulating-cell-free-dna-as-biomarkers-for-the-early-detection-of-cancer
#6
REVIEW
Junyun Wang, Xiao Han, Yingli Sun
Detecting cell-free DNA (cfDNA) or circulating tumor DNA (ctDNA) in plasma or serum could serve as a "liquid biopsy", which would be useful for numerous diagnostic applications. cfDNA methylation detection is one of the most promising approaches for cancer risk assessment. Here, we reviewed the literature related to the use of serum or plasma circulating cell-free DNA for cancer diagnosis in the early stage and their power as future biomarkers.
January 5, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28060757/line-1-hypomethylation-status-of-circulating-cell-free-dna-in-plasma-as-a-biomarker-for-colorectal-cancer
#7
Yuzo Nagai, Eiji Sunami, Yoko Yamamoto, Keisuke Hata, Satoshi Okada, Koji Murono, Koji Yasuda, Kensuke Otani, Takeshi Nishikawa, Toshiaki Tanaka, Tomomichi Kiyomatsu, Kazushige Kawai, Hiroaki Nozawa, Soichiro Ishihara, Dave S B Hoon, Toshiaki Watanabe
Colorectal cancer (CRC) is a serious public health problem and non-invasive biomarkers improving diagnosis or therapy are strongly required. Circulating cell-free DNA (cfDNA) has been a promising target for this purpose. In this study, we evaluated the potential of long interspersed nuclear element-1 (LINE-1) hypomethylation as a blood biomarker for CRC. LINE-1 hypomethylation level in plasma cfDNA in 114 CRC patients was retrospectively examined by absolute quantitative analysis of methylated alleles real-time PCR, and was expressed using LINE-1 hypomethylation index (LHI) [unmethylated copy number/ (methylated copy number + unmethylated copy number)]...
January 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28056555/a-prospective-clinical-trial-to-compare-the-performance-of-dried-blood-spots-prenatal-screening-for-down-s-syndrome-with-conventional-non-invasive-testing-technology
#8
Huiying Hu, Yulin Jiang, Minghui Zhang, Shanying Liu, Na Hao, Jing Zhou, Juntao Liu, Xiaojin Zhang, Liangkun Ma
To evaluate, side by side, the efficiency of dried blood spots (DBSs) against serum screening for Down's syndrome, and then, to construct a two-tier strategy by topping up the fetal cell-free DNA (cfDNA) secondary screening over the high-risk women marked by the primary blood testing to build a practical screening tactic to identify fetal Down's syndrome. One thousand eight hundred and thirty-seven low-risk Chinese women, with singleton pregnancy, were enrolled for the study. Alpha-fetoprotein and free beta human chorionic gonadotropin were measured for the serum as well as for the parallel DBS samples...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28056336/the-clinical-role-of-circulating-free-tumor-dna-in-gastrointestinal-malignancy
#9
REVIEW
Jessica A Howell, Shahid A Khan, Susanne Knapp, Mark R Thursz, Rohini Sharma
Circulating cell-free DNA (cfDNA) is DNA released from necrotic or apoptotic cells into the bloodstream. While both healthy cells and cancer cells release cfDNA, tumors are associated with higher levels of tumor-derived circulating cell-free DNA (ctDNA) detectable in blood. Absolute levels of ctDNA and its genetic mutations and epigenetic changes show promise as potentially useful biomarkers of tumor biology, progression, and response to therapy. Moreover, studies have demonstrated the discriminative accuracy of ctDNA levels for diagnosis of gastrointestinal cancer compared with benign inflammatory diseases...
December 22, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28052016/total-dna-input-is-a-crucial-determinant-of-the-sensitivity-of-plasma-cell-free-dna-egfr-mutation-detection-using-droplet-digital-pcr
#10
Yu Zhang, Yan Xu, Wei Zhong, Jing Zhao, Minjiang Chen, Li Zhang, Longyun Li, Mengzhao Wang
We evaluated the use of droplet digital PCR (ddPCR) to detect plasma cell-free DNA (cfDNA) epidermal growth factor receptor (EGFR) mutations in advanced non-small cell lung cancer (NSCLC) patients. Compared with tumor-tissue-based detection, the sensitivity of ddPCR for detecting plasma cfDNA tyrosine kinase inhibitor (TKI)-sensitizing EGFR mutations was 61.3%, the specificity was 96.7%, and the consistency rate was 81.4% (κ=0.605, 95% confidence interval: 0.501-0.706, p <0.0001). The sensitivity declined from 82...
December 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/28046008/cell-free-dna-provides-a-good-representation-of-the-tumor-genome-despite-its-biased-fragmentation-patterns
#11
Xiangyuan Ma, Liangjun Zhu, Xue Wu, Hua Bao, Xiaonan Wang, Zhili Chang, Yang W Shao, Zhenxin Wang
Cell-free DNA (cfDNA) is short, extracellular, fragmented double-stranded DNA found in plasma. Plasma of patients with solid tumor has been found to show significantly increased quantities of cfDNA. Although currently poorly understood, the mechanism of cfDNA generation is speculated to be a product of genomic DNA fragmentation during cellular apoptosis and necrosis. Sequencing of cfDNA with tumor origin has identified tumor biomarkers, elucidating molecular pathology and assisting in accurate diagnosis. In this study, we performed whole-genome sequencing ofcfDNA samples with matching tumor and whole blood samples from five patients diagnosed with stage IV gastric or lung cancer...
2017: PloS One
https://www.readbyqxmd.com/read/28035516/circadian-rhythm-of-methylated-septin-9-cell-free-dna-amount-and-tumor-markers-in-colorectal-cancer-patients
#12
Kinga Tóth, Árpád V Patai, Alexandra Kalmár, Barbara Kinga Barták, Zsófia Brigitta Nagy, Orsolya Galamb, Barnabás Wichmann, Zsolt Tulassay, Béla Molnár
To determine the level of cell-free DNA (cfDNA), Septin 9 (SEPT9) and tumor markers (CEA, AFP, CA19-9, TPA, CA72-4). Plasma samples were collected four times a day (06:00, 12:00, 18:00, 24:00) from 9 patients with CRC (5 stage I-II, 4 stage III-IV), from one with colorectal adenoma and from one healthy control. CfDNA was isolated, quantified and bisulfite-converted. CfDNA and methylated SEPT9 were determined by RT-PCR. Plasma levels of conventional tumor markers were also measured. The lowest cfDNA concentrations were observed at 24:00 and 18:00 in stage I-III patients...
December 30, 2016: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28034880/polyclonal-secondary-fgfr2-mutations-drive-acquired-resistance-to-fgfr-inhibition-in-patients-with-fgfr2-fusion-positive-cholangiocarcinoma
#13
Lipika Goyal, Supriya K Saha, Leah Y Liu, Giulia Siravegna, Ignaty Leshchiner, Leanne G Ahronian, Jochen K Lennerz, Phuong Vu, Vikram Deshpande, Avinash Kambadakone, Benedetta Mussolin, Stephanie Reyes, Laura Henderson, Jiaoyuan Elisabeth Sun, Emily E Van Seventer, Joseph M Gurski, Sabrina Baltschukat, Barbara Schacher-Engstler, Louise Barys, Christelle Stamm, Pascal Furet, David P Ryan, James R Stone, A John Iafrate, Gad Getz, Diana Graus Porta, Ralph Tiedt, Alberto Bardelli, Dejan Juric, Ryan B Corcoran, Nabeel Bardeesy, Andrew X Zhu
Genetic alterations in the fibroblast growth factor receptor (FGFR) pathway are promising therapeutic targets in many cancers, including intrahepatic cholangiocarcinoma (ICC). The FGFR inhibitor BGJ398 displayed encouraging efficacy in patients with FGFR2 fusion-positive ICC in a phase II trial, but the durability of response was limited in some patients. Here, we report the molecular basis for acquired resistance to BGJ398 in three patients via integrative genomic characterization of cell-free circulating tumor DNA (cfDNA), primary tumors, and metastases...
December 29, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/28029553/somatic-mutation-detection-using-various-targeted-detection-assays-in-paired-samples-of-circulating-tumor-dna-primary-tumor-and-metastases-from-patients-undergoing-resection-of-colorectal-liver-metastases
#14
Nick Beije, Jean C Helmijr, Marjolein J A Weerts, Corine M Beaufort, Matthew Wiggin, Andre Marziali, Cornelis Verhoef, Stefan Sleijfer, Maurice P H M Jansen, John W M Martens
Assessing circulating tumor DNA (ctDNA) is a promising method to evaluate somatic mutations from solid tumors in a minimally-invasive way. In a group of twelve metastatic colorectal cancer (mCRC) patients undergoing liver metastasectomy, from each patient DNA from cell-free DNA (cfDNA), the primary tumor, metastatic liver tissue, normal tumor-adjacent colon or liver tissue, and whole blood were obtained. Investigated was the feasibility of a targeted NGS approach to identify somatic mutations in ctDNA. This targeted NGS approach was also compared with NGS preceded by mutant allele enrichment using synchronous coefficient of drag alteration technology embodied in the OnTarget assay, and for selected mutations with digital PCR (dPCR)...
October 10, 2016: Molecular Oncology
https://www.readbyqxmd.com/read/28027320/genomic-analysis-of-uterine-lavage-fluid-detects-early-endometrial-cancers-and-reveals-a-prevalent-landscape-of-driver-mutations-in-women-without-histopathologic-evidence-of-cancer-a-prospective-cross-sectional-study
#15
Navya Nair, Olga Camacho-Vanegas, Dmitry Rykunov, Matthew Dashkoff, Sandra Catalina Camacho, Cassie A Schumacher, Jonathan C Irish, Timothy T Harkins, Elijah Freeman, Isaac Garcia, Elena Pereira, Sviatoslav Kendall, Rachel Belfer, Tamara Kalir, Robert Sebra, Boris Reva, Peter Dottino, John A Martignetti
BACKGROUND: Endometrial cancer is the most common gynecologic malignancy, and its incidence and associated mortality are increasing. Despite the immediate need to detect these cancers at an earlier stage, there is no effective screening methodology or protocol for endometrial cancer. The comprehensive, genomics-based analysis of endometrial cancer by The Cancer Genome Atlas (TCGA) revealed many of the molecular defects that define this cancer. Based on these cancer genome results, and in a prospective study, we hypothesized that the use of ultra-deep, targeted gene sequencing could detect somatic mutations in uterine lavage fluid obtained from women undergoing hysteroscopy as a means of molecular screening and diagnosis...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/28010185/methodological-biological-and-clinical-aspects-of-circulating-free-dna-in-metastatic-colorectal-cancer
#16
REVIEW
Karen-Lise G Spindler
BACKGROUND: Circulating DNA can be used to measure the total cell-free DNA (cfDNA) and for detection and quantification of tumor-specific genetic alterations in the peripheral blood, and the broad clinical potential of circulating DNA has attracted increasing focus over the past decade. Concentrations of circulating DNA are high in metastatic colorectal cancer (CRC), and the total levels of cfDNA have been reported to hold strong prognostic value. Colorectal tumors are characterized by a high frequency of well known, clinically relevant genetic alteration, which is readily detected in the cfDNA and holds potential for tailoring of palliative therapy and for monitoring during treatment...
January 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28006816/egfr-mutation-detection-in-circulating-cell-free-dna-of-lung-adenocarcinoma-patients-analysis-of-lux-lung-3-and-6
#17
Yi-Long Wu, Lecia V Sequist, Cheng-Ping Hu, Jifeng Feng, Shun Lu, Yunchao Huang, Wei Li, Mei Hou, Martin Schuler, Tony Mok, Nobuyuki Yamamoto, Kenneth O'Byrne, Vera Hirsh, Neil Gibson, Dan Massey, Miyoung Kim, James Chih-Hsin Yang
BACKGROUND: In the Phase III LUX-Lung 3/6 (LL3/LL6) trials in epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma patients, we evaluated feasibility of EGFR mutation detection using circulating cell-free DNA (cfDNA) and prognostic and predictive utility of cfDNA positivity (cfDNA+). METHODS: Paired tumour and blood samples were prospectively collected from randomised patients. Mutations were detected using cfDNA from serum (LL3) or plasma (LL6) by a validated allele-specific quantitative real-time PCR kit...
January 17, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28003743/prognostic-utility-of-admission-cell-free-dna-levels-in-patients-with-chronic-obstructive-pulmonary-disease-exacerbations
#18
Avital Avriel, Dmitry Rozenberg, Yael Raviv, Dov Heimer, Amir Bar-Shai, Rachel Gavish, Jony Sheynin, Amos Douvdevani
BACKGROUND: Chronic obstructive pulmonary disease exacerbations (COPDEs) are associated with increased morbidity and mortality. Cell-free DNA (cfDNA) is a novel biomarker associated with clinical outcomes in several disease states but has not been studied in COPD. The objectives of this study were to assess cfDNA levels during a COPDE, to evaluate the association of cfDNA with clinical parameters and to explore the prognostic implications of cfDNA levels on long-term survival. METHODS: This was an observational study that assessed cfDNA levels in patients admitted to hospital for a COPDE...
2016: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/28003276/lesion-directed-therapies-and-monitoring-tumor-evolution-using-liquid-biopsies
#19
Mariangela Russo, Alberto Bardelli
Precision oncology relies on targeted drugs, such as kinase inhibitors, that are presently administered based on molecular profiles obtained from surgical or bioptic tissue samples. The inherent ability of human tumors to molecularly evolve in response to drug pressures represents a daunting diagnostic challenge. Circulating free DNA (cfDNA) released from primary and metastatic lesions can be used to draw molecular maps that can be continuously updated to match each tumor's evolution. We will present evidence that liquid biopsies can effectively interrogate how targeted therapies drive lesion-specific drug-resistance mechanisms...
December 21, 2016: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/27999323/circulating-cell-free-dna-levels-could-predict-oncological-outcomes-of-patients-undergoing-esophagectomy-for-esophageal-squamous-cell-carcinoma
#20
Chih-Cheng Hsieh, Han-Shui Hsu, Shih-Ching Chang, Yann-Jang Chen
Circulating cell-free DNA (cfDNA) is a potential biomarker for cancer progression but its role is unclear in patients with esophageal squamous cell carcinoma (ESCC) after esophagectomy. We investigated relationships between plasma cfDNA levels and clinicopathological parameters in ESCC patients. Eighty-one ESCC patients who received esophagectomy were enrolled. Plasma samples from these patients and 95 normal controls were collected. DNA copy numbers were measured by real-time quantitative PCR. Subjects were divided into two groups by cfDNA level...
December 17, 2016: International Journal of Molecular Sciences
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